Capsaicin: A chili pepper bioactive phytocompound with a potential role in suppressing cancer development and progression.

Cancer profoundly influences morbidity and fatality rates worldwide. Patients often have dismal prognoses despite recent improvements in cancer therapy regimens. However, potent biomolecules derived from natural sources, including medicinal and dietary plants, contain biological and pharmacological properties to prevent and treat various human malignancies. Capsaicin is a bioactive phytocompound present in red hot chili peppers. Capsaicin has demonstrated many biological effects, including antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic capabilities. This review highlights the cellular and molecular pathways through which capsaicin exhibits antineoplastic activities. Our work also depicts the synergistic anticancer properties of capsaicin in conjunction with other natural bioactive components and approved anticancer drugs. Capsaicin inhibits proliferation in various cancerous cells, and its antineoplastic actions in numerous in vitro and in vivo carcinoma models impact oncogenesis, tumor-promoting and suppressor genes, and associated signaling pathways. Capsaicin alone or combined with other phytocompounds or approved antineoplastic drugs triggers cell cycle progression arrest, generating reactive oxygen species and disrupting mitochondrial membrane integrity, ultimately stimulating caspases and promoting death. Furthermore, capsaicin alone or in combination can promote apoptosis in carcinoma cells by enhancing the p53 and c-Myc gene expressions. In conclusion, capsaicin alone or in combination can have enormous potential for cancer prevention and intervention, but further high-quality studies are needed to firmly establish the clinical efficacy of this phytocompound.

Peanut (Arachis hypogaea L.) seeds and by-products in metabolic syndrome and cardiovascular disorders: A systematic review of clinical studies.

BACKGROUND: Cardiovascular disease (CVDs) is the leading cause of death worldwide. The main risk factors are hypertension, diabetes, obesity, and increased serum lipids. The peanut (Arachis hypogaea L.), also known as the groundnut, goober, pindar, or monkey nut, belongs to the Fabaceae family and is the fourth most cultivated oilseed in the world. The seeds and skin of peanuts possess a rich phytochemical profile composed of antioxidants, such as phenolic acids, stilbenes, flavonoids, and phytosterols. Peanut consumption can provide numerous health benefits, such as anti-obesity, antidiabetic, antihypertensive, and hypolipidemic effects. Accordingly, peanuts have the potential to treat CVD and counteract its risk factors. PURPOSE: This study aims to critically evaluate the effects of peanuts on metabolic syndrome (MetS) and CVD risk factors based on clinical studies. METHOD: This review includes studies indexed in MEDLINE-PubMed, COCHRANE, and EMBASE, and the Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were adhered to. RESULTS: Nineteen studies were included and indicated that the consumption of raw peanuts or differing forms of processed foods containing peanut products and phytochemicals could improve metabolic parameters, such as glycemia, insulinemia, glycated hemoglobin, lipids, body mass index, waist circumference, atherogenic indices, and endothelial function. CONCLUSION: We propose that this legume and its products be used as a sustainable and low-cost alternative for the prevention and treatment of MetS and CVD. However, further research with larger sample sizes, longer intervention durations, and more diverse populations is needed to understand the full benefit of peanut consumption in MetS and CVD.

Targeting transforming growth factor-ß signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin.

BACKGROUND: Cancer is the world's second leading cause of death, but a significant advancement in cancer treatment has been achieved within the last few decades. However, major adverse effects and drug resistance associated with standard chemotherapy have led towards targeted treatment options. OBJECTIVES: Transforming growth factor-ß (TGF-ß) signaling plays a key role in cell proliferation, differentiation, morphogenesis, regeneration, and tissue homeostasis. The prime objective of this review is to decipher the role of TGF-ß in oncogenesis and to evaluate the potential of various natural and synthetic agents to target this dysregulated pathway to confer cancer preventive and anticancer therapeutic effects. METHODS: Various authentic and scholarly databases were explored to search and obtain primary literature for this study. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria was followed for the review. RESULTS: Here we provide a comprehensive and critical review of recent advances on our understanding of the effect of various bioactive natural molecules on the TGF-ß signaling pathway to evaluate their full potential for cancer prevention and therapy. CONCLUSION: Based on emerging evidence as presented in this work, TGF-ß-targeting bioactive compounds from natural sources can serve as potential therapeutic agents for prevention and treatment of various human malignancies.

Pediatric acute lymphoblastic leukemia management using multitargeting bioactive natural compounds: A systematic and critical review.

Pediatric acute lymphoblastic leukemia (pALL), a malignancy of the lymphoid line of blood cells, accounts for a large percentage of all childhood leukemia cases. Although the 5-year survival rate for children with ALL has greatly improved over years, using chemotherapeutics as its first-line treatment still causes short- and long-term side effects. Furthermore, induction of toxicity and resistance, as well as the high cost, limit their application. Phytochemicals, with remarkable cancer preventive and chemotherapeutic characteristics, may serve as old solutions to new challenges. Bioactive plant secondary metabolites have exhibited promising antileukemic and adjunctive effects by targeting various molecular processes, including autophagy, cell cycle, angiogenesis, and extrinsic/intrinsic apoptotic pathways. Although numerous reports have shown that various plant secondary metabolites can interfere with the progression of malignancies, including leukemia, there was no comprehensive review article on the effect of phytochemicals on pALL. This systematic review aims to provide critical and cohesive analysis of the potential of various naturally-occurring plant secondary metabolites in the management of pALL with the understanding of underlying molecular and cellular mechanisms of action.

Natural products targeting the PI3K-Akt-mTOR signaling pathway in cancer: A novel therapeutic strategy.

The phosphatidylinositol 3-kinase (PI3K)-Akt and the mammalian target of rapamycin (mTOR) represent two vital intracellular signaling pathways, which are associated with various aspects of cellular functions. These functions play vital roles in quiescence, survival, and growth in normal physiological circumstances as well as in various pathological disorders, including cancer. These two pathways are so intimately connected to each other that in some instances these are considered as one unique pathway crucial for cell cycle regulation. The purpose of this review is to emphasize the role of PI3K-Akt-mTOR signaling pathway in different cancer conditions and the importance of natural products targeting the PI3K-Akt-mTOR signaling pathway. This review also aims to draw the attention of scientists and researchers to the assorted beneficial effects of the numerous classes of natural products for the development of new and safe drugs for possible cancer therapy. We also summarize and critically analyze various preclinical and clinical studies on bioactive compounds and constituents, which are derived from natural products, to target the PI3K-Akt-mTOR signaling pathway for cancer prevention and intervention.

Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention.

The phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of the rapamycin (mTOR)-signaling pathway has been suggested to have connections with the malignant transformation, growth, proliferation, and metastasis of various cancers and solid tumors. Relevant connections between the PI3K/Akt/mTOR pathway, cell survival, and prostate cancer (PC) provide a great therapeutic target for PC prevention or treatment. Recent studies have focused on small-molecule mTOR inhibitors or their usage in coordination with other therapeutics for PC treatment that are currently undergoing clinical testing. In this study, the function of the PI3K/Akt/mTOR pathway, the consequence of its dysregulation, and the development of mTOR inhibitors, either as an individual substance or in combination with other agents, and their clinical implications are discussed. The rationale for targeting the PI3K/Akt/mTOR pathway, and specifically the application and potential utility of natural agents involved in PC treatment is described. In addition to the small-molecule mTOR inhibitors, there are evidence that several natural agents are able to target the PI3K/Akt/mTOR pathway in prostatic neoplasms. These natural mTOR inhibitors can interfere with the PI3K/Akt/mTOR pathway through multiple mechanisms; however, inhibition of Akt and suppression of mTOR 1 activity are two major therapeutic approaches. Combination therapy improves the efficacy of these inhibitors to either suppress the PC progression or circumvent the resistance by cancer cells.

The phytochemical, biological, and medicinal attributes of phytoecdysteroids: An updated review.

The phytoecdysteroids (PEs) comprise a large group of biologically-active plant steroids, which have structures similar to those of insect-molting hormones. PEs are distributed in plants as secondary metabolites that offer protection against phytophagus (plant-eating) insects. When insects consume the plants containing these chemicals, they promptly molt and undergo metabolic destruction; the insects eventually die. Chemically, ecdysteroids are a group of polyhydroxylated ketosteroids that are structurally similar to androgens. The carbon skeleton of ecdysteroids is termed as cyclopentanoperhydro-phenanthrene with a ß-side chain at carbon-17. The essential characteristics of ecdysteroids are a cis-(5ß-H) junction of rings A and B, a 7-en-6-one chromophore, and a trans-(14α-OH) junction of rings C and D. Plants only synthesize PEs from mevalonic acid in the mevalonate pathway of the plant cell using acetyl-CoA as a precursor; the most common PE is 20-hydroxyecdysone. So far, over 400 PEs have been identified and reported, and a compilation of 166 PEs originating from 1998 has been previously reviewed. In the present review, we have summarized 212 new PEs reported between 1999 and 2019. We have also critically analyzed the biological, pharmacological, and medicinal properties of PEs to understand the full impact of these phytoconstituents in health and disease.